The project proposed here is a combined clinical and laboratory investigation of recombinant interleukin-4 (IL-4) in patients with metastatic melanoma. We postulate that the immunomodulatory effects of IL-4, particularly its effects on cytotoxic T lymphocytes, may mediate tumor regression and thereby exert a beneficial effect in these patients with a malignancy that is invariably fatal. We believe that cytotoxic T lymphocytes are critical effector cells involved in an antineoplastic immune response. Preclinical studies suggest that IL-4 may selectively expand antigen specific cytotoxic T lymphocytes from tumor infiltrating lymphocytes, with reactivity against autologous melanoma. We plan to treat twenty five patients with metastatic melanoma over one ye Patients with cutaneous or nodal disease with or without visceral involvement will be preferentially selected to provide tumor specimens for the proposed laboratory studies. Before, during, and after IL-4 therapy, patients will be evaluated for response and toxicity. In addition, we will examine the relationship between IL-4 'induced immunomodulation and antineoplastic activity by: 1) determining the effects of IL-4 on circulating immune effector cells in terms of phenotype, cytotoxicity, and proliferative activity, and 2) evaluating TIL cytotoxicity, specificity and phenotype from pre and post therapy tumor biopsies. Because IL-4 has activity on B cells, an analysis of IL-4 effects on antimelanoma antibody production is also planned. Central to this project is a well established group of collaborators dedicated to investigating malignant melanoma, clinically and in the laboratory. The proposed study represents an extension of our interests in novel approaches to the treatment of malignant melanoma. The results of this study will further expand our knowledge of the therapeutic and biologic effects of IL-4 and will characterize the role of cytotoxic T lymphocytes in mediating tumor regression. Hopefully, this work will lead to antimelanoma therapeutic strategies for this most resistant disease.